Abstract Diarrheal diseases are the among the leading cause of death in children worldwide, most of which occur in low-income countries. In high-income countries, pediatric diarrhea remains a major utilization of healthcare resources. Treatment of diarrhea is mostly empiric, with antibiotic use mostly based on clinical suspicion for bacterial causes. However, the majority of cases of diarrhea do not benefit from antibiotic use, and inappropriate use leads to toxicity and resistance. Furthermore, despite the increasing availability of rapid molecular testing, there is little data to base a decision of whom or when to test. Our overarching goal is to develop and validate clinical decision tools for management of diarrheal illnesses in children of both high and low resource settings. We will utilize prospectively-collected data from two recently-completed multicenter cohort studies of pediatric diarrhea. These studies feature extensive etiologic testing, well-characterized clinical elements, and longitudinal outcome data. We have assembled a team with expertise in pediatric diarrhea, clinical prediction rules, and machine learning methods. In Aim 1, we will use domestic data to develop and validate: a) a score for bacterial etiology, and b) a score for which patients are likely to benefit from further testing. We will derive the scores using data from IMPACT, an NIH-sponsored study of 1200 children from 5 US Emergency Departments, and validate using electronic health records from the Utah Intermountain Health System. In Aim 2, we will use international data to develop and validate: a) a diagnostic score for bacterial etiology, and b) a prognostic score for risk stratification of children who go on to poor outcomes. We will derive the scores using data from GEMS, a study of over 9400 children across 7 low-resource countries, and validate using VIDA study of children in 3 African countries. Completion of the Aims will result in the availability of a number of clinical tools that healthcare workers worldwide can use for evidence-based care of children with diarrhea.